Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ion channels in beta cells regulate electrical and secretory activity in response to metabolic, pharmacologic, or neural signals by controlling the permeability to K+ and Ca2+. The ATP-sensitive K+ channels act as a switch that responds to fuel secretagogues or sulfonylureas to initiate depolarization. This depolarization opens voltage-dependent calcium channels (VDCC) to increase the amplitude of free cytosolic Ca2+ levels ([Ca2+]i), which triggers exocytosis. Acetyl choline and vasopressin (VP) both potentiate the acute effects of glucose on insulin secretion by generating inositol 1,4,5-trisphosphate to release intracellular Ca2+; VP also potentiates sustained insulin secretion by effects on depolarization. In contrast, inhibitors of insulin secretion decrease [Ca2+]i by either hyperpolarizing the beta cell or by receptor-mediated, G-protein-coupled effects to decrease VDCC activity. Repolarization is initiated by voltage- and Ca(2+)-activated K+ channels. A human insulinoma voltage-dependent K+ channel cDNA was recently cloned and two types of alpha 1 subunits of the VDCC have been identified in insulin-secreting cell lines. Determining how ion channels regulate insulin secretion in normal and diabetic beta cells should provide pathophysiologic insight into the beta cell signal transduction defect characteristic of non-insulin dependent diabetes (NIDDM).
 ...
PMID:The role of ion channels in insulin secretion. 138 42

Red cell phosphoglycerate kinase (PGK) activity was determined in normal individuals and patients with, type I (insulin-dependent) diabetes and insulin treated diabetes. The PGK activity was significantly (P less than 0.001) elevated in diabetes, however it is restored to normalcy after insulin treatment (normal 282.54 +/- 9.46, type I diabetic 342.06 +/- 6.24, insulin treated diabetic 292.66 +/- 7.12 IU/g haemoglobin at 37 degrees C). No significant alteration was observed in the percentage of PGK bound to the membrane fraction of red cells in all the three conditions. The results indicate that the increased PGK activity is a result of a regulatory mechanism induced by the fluctuation of ATP level in response to elevated Na:K pump rate of erythrocytes in type I diabetes mellitus.
 ...
PMID:Red cell phosphoglycerate kinase in insulin-dependent diabetes mellitus. 218 28

Knowledge of the metabolic changes that occur in insulin-resistant type 2 diabetes is relatively lacking compared to insulin-deficient type 1 diabetes. This paper summarizes the importance of the C57BL/KsJ-db/db mouse as a model of type 2 diabetes, and illustrates the effects that insulin-deficient and insulin-resistant states have on hepatic glycogen metabolism. A longitudinal study of db/db mice of ages 2-15 weeks revealed that significant changes in certain parameters of hepatic glycogen metabolism occur during this period. The liver glycogen levels were similar between diabetic and control mice. However, glycogen particles from db/db mice were on average smaller in mass and had shorter exterior and interior chain lengths. Total phosphorylase and phosphorylase a activities were elevated in the genetically diabetic mice. This was primarily due to an increase in the amount of enzymic protein apparently the result of a decreased rate of degradation. It was not possible to find a consistent alteration in glycogen activity in the db/db mice. Glycogen synthase and phosphorylase from diabetic liver revealed some changes in kinetic properties in the form of a decrease in Vmax and altered sensitivity to inhibitors like ATP. The altered glycogen structure in db/db mice may have contributed to changes in the activities and properties of glycogen synthase and phosphorylase. The exact role played by hormones (insulin and glucagon) in these changes is not clear but further studies should reveal their contributions. The db/db mouse provides a good model for type 2 diabetes and for fluctuating insulin and glucagon ratios.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hepatic glycogen metabolism in the db/db mouse. 240 41

Diabetes mellitus children demonstrate the lowering of insulin binding by lymphocytes on appearance of the signs of insulin overdosage. After standard breakfast preceded by insulin injection such patients show a lower blood content of ATP as compared to children without metabolic signs of insulin overdosage, which may be of importance in the pathogenesis of insulin resistance development. Patients with type I diabetes mellitus and hyperlactatemia manifested the lowering of glucose assimilation by lymphocytes whatever the presence of the signs of insulin overdosage, pointing to insulin resistance.
 ...
PMID:[State of insulin receptors and carbohydrate metabolism in children with diabetes mellitus]. 269 79

Enzymatic systems of hepatic hyperlipogenesis supply by substrate (acetyl-CoA) and cofactors (NADPH and ATP) were studied in experiments on diabetic C57Bl/Ks J mice (db/db) that served as a model of non-insulin dependent diabetes. The rise in acetyl-CoA synthetase activity catalyzing the primary step of lipogenesis from acetate has been found, while pyruvate dehydrogenase complex activity did not differ from the control and ATP-citrate lyase activity was lowered. Hyperlipogenesis in non-insulin dependent diabetes was induced by the activation of cellular energy supply revealed in enhanced 2-oxoglutarate dehydrogenase activity and elevated ATP level, as well as changes in the activity ratio of NADPH supply and utilization and the rise in fructose-1,6-diphosphate, allosteric effector of fatty acid synthetase, which resulted in the increase of the enzyme activity and created wider potentials of NADPH utilization as a reducing equivalent in lipogenesis.
 ...
PMID:[Enzyme systems of the substrate and cofactor supply of hyperlipogenesis in non-insulin-dependent diabetes]. 289 64

Nitric oxide produced by inducible nitric oxide synthase in islets exerts inhibitory and cytotoxic effects on pancreatic beta cells and is therefore thought to be a potent mediator in the pathogenesis of Type I diabetes mellitus. Here, using isolated rat pancreatic islets, we show that high-concentration nicotinamide (20 mM), but not low-concentration nicotinamide (5 mM), attenuates the interleukin-1 beta-evoked inhibition of glucose-induced insulin secretion by preventing the induction of interferon regulatory factor-1, a transcriptional factor which plays an essential role in inducible nitric oxide synthase gene expression, and the interleukin-1 beta-induced nitric oxide formation. High-concentration nicotinamide also restored an interleukin-1 beta-induced decrease in ATP content in pancreatic beta cells, suggesting that interleukin-1 beta-induced nitric oxide inhibits the mitochondrial function. The present results show the molecular basis of the preventive effect of high-dose nicotinamide on Type I diabetes mellitus.
 ...
PMID:Nicotinamide inhibits IRF-1 mRNA induction and prevents IL-1 beta-induced nitric oxide synthase expression in pancreatic beta cells. 748 87

A decreased insulin response, preferentially to glucose, has been considered a hallmark of non-insulin dependent diabetes mellitus (Type 2) in humans. Syndromes resembling human diabetes occur spontaneously in many animal species and can also be induced by treating animals with drugs or viruses, excising their pancreases or manipulating their diet. Among these models, rat diabetes induced by neonatal streptozotocin administration (n-STZ models) has been first recognized as an adequate tool to study the long-term consequences of a gradually reduced beta-cell mass. More recently, the GK (Goto Kakisaki) Wistar rat has become available and is now considered as a promising spontaneous rat model of non-insulin dependent diabetes. We and others have found that defects in insulin secretion and action develop in the n-STZ and the GK models, which in many ways resemble those described in human non-insulin dependent diabetes. This review is aimed to sum up with a comparative approach, the informations so far collected in the n-STZ and GK models concerning the cellular mechanisms leading to the desensitization of their beta-cells to glucose. Taken together, the data reinforce the view that the impairment of glucose-induced insulin release in n-STZ and GK rats is clearly related to a defect in oxidative glycolysis. This leads to a severe decrease in the mitochondrial oxidative catabolism of glucose-derived pyruvate. Its coincides with a lower ATP/ADP ratio in glucose-stimulated islets and a subsequent alteration of ionic events tightly coupled to the fuel function of the hexose in islet cells, i.e. the decrease in K+ conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Glucose refractoriness of pancreatic beta-cells in rat models of non-insulin dependent diabetes. 780 48

Comparisons of soluble and bound GAD activities in brain, pancreas, and kidneys were performed. In all three organs GAD was present in three forms: soluble GAD; GAD, the solubility of which was achievable by means of CHAPS detergent; and GAD, refractory towards the detergent affect. The activity of these three GAD fractions, each belonging to a different cellular compartment, proportionally differed. The ratio of free, bound, and irreversibly bound activity expressed in percentage was 63:21:15 in the brain, and 14:40:36 in the pancreas. In coincidence with the occurrence of autoantibodies to GAD from the brain under the condition of SMS, and that from the pancreatic beta-cells under the condition of IDDM, it is supposed that the conditions favourable for the origin of the immune response are rendered by GAD bound in membranes. In kidneys the proportions of free (15%) and bound GAD (29%) are complicated by until now unassessed factors, since their isolation from the free, eventually bound GAD causes an activity waste of 50% which supervenes following the homogenate separation by the use of centrifuge. Effect of ATP and chlorides displays both, different and common properties of GAD from the mentioned three organs. ATP inhibited the brain GAD and the renal supernatant GAD, whereas it activated GAD from the homogenate and sediment of the kidneys and the pancreatic GAD. Chlorides inhibited the brain and pancreatic GAD and activated the renal GAD. (Fig. 8, Tab. 1, Ref. 16.).
 ...
PMID:[Glutamic acid decarboxylase in the brain, pancreas and kidneys. Comparison of its properties]. 800 91

Na+/K(+)- and Ca(2+)-ATPase are the major ATP-dependent membrane-bound enzymes that regulate the cation transmembrane gradient which is altered both in red blood cell (RBC) senescence and in RBCs of diabetic patients. In an attempt to clarify the possible connection between diabetes mellitus and ageing, we investigated the relationship between RBC ATP content, Na+/K(+)-ATPase, Ca(2+)-ATPase activities and ageing in healthy, insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) subjects. A significant correlation was found (r = -0.82; P < 0.001) between RBC ATP content and subject's age only in the control group. A significant reduction in Na+/K(+)-ATPase activity was observed in the older group (C2) of control subjects, in comparison with the younger (C1) one. In both IDDM and NIDDM subjects, the enzymatic activity was significantly decreased when compared with health subjects of similar age (P < 0.001). A significant negative correlation was found between age and enzymatic activity in healthy subjects (r = -0.60; P < 0.001). No difference was observed in the RBC membrane Ca(2+)-ATPase activity between younger (C1) and older (C2) healthy subjects. Ca(2+)-ATPase activity was significantly increased both in IDDM patients compared with C1 (P < 0.001) and in NIDDM patients compared with C2 (P < 0.001). The present data indicate that ageing causes a reduction in the erythrocyte ATP content in both healthy and diabetic subjects. In diabetic patients Na+/K(+)-ATPase activity decreases independently of age.
 ...
PMID:Diabetes mellitus and subjects' ageing: a study on the ATP content and ATP-related enzyme activities in human erythrocytes. 913 82

In order to reveal sequel of events responsible for increase in red cell cytosolic glucose-6 phosphate (G-6P) content of diabetic patients the enzyme producing and transforming G-6P were assayed. Increase in the activity of hexokinase and decrease in phosphoglucoisomerase activity was observed in mild insulin dependent diabetes mellitus (mIDDM) rat erythrocytes. Increase and decrease in activity of hexokinase and phosphoglucoisomerase respectively will increase the cytosolic glucose-6 phosphate content. Thus any substance which autoregulate the activity of hexokinase and maintains critical level of G-6P necessary for generation of ATP and coenzymes (NADPH & NAD+) in the prevailing hyperglycemic state can be a potential therapeutic agent for diabetic patients.
 ...
PMID:Activation of hexokinase by mild insulin dependent diabetes mellitus in rat erythrocytes. 937 21


1 2 3 4 5 6 7 8 9 10 Next >>